Many illnesses or conditions require administration of a constant or sustained level of a medicament or biologically active agent to provide the desired prophylactic or therapeutic effect. This may be accomplished through a multiple dosing regimen or by employing a system that releases the medicament in a sustained fashion.
Attempts to sustain medication levels include the use of biodegradable materials, such as polymeric matrices, containing the medicament. The use of these matrices, for example, in the form of microparticles or microcarriers, can provide sustained release of medicaments by utilizing the inherent biodegradability of the polymer. The ability to provide a sustained level of medicament can result in improved patient compliance. For example, patient compliance can be particularly difficult in the treatment of affective disorders such as schizophrenia, depression, anxiety and in view of the large outpatient population and altered psychological state of the patient.
Certain methods of fabricating polymer-based sustained release devices comprise the steps of dissolving a polymer in a solvent, adding to the polymer solution the active agent to be incorporated and removing the solvent from the mixture, thereby forming a matrix of the polymer with the active agent distributed throughout the matrix. However, the physical characteristics of the microparticles, for example, the morphology, density and size, are significantly dependent upon all steps used in the method of preparation making control and tailoring of the physical characteristics of the resulting microparticles a difficult (sometimes impossible) and expensive undertaking.
For example, many sustained release compositions can exhibit an increased release of biologically active agent over the first twenty-four hours after administration, commonly referred to as a burst. In some instances, this burst can result in an undesirable increase in the levels of biologically active agent and/or minimal release of agent thereafter. Tailoring of the physical characteristics of the microparticles to provide an improved release can require modification of the entire process of preparation. Therefore, a need exists for methods of preparing sustained release microparticles where additional control over release kinetics by, for example, reducing the burst of agent and/or providing an improved release profile can be exerted.